The slides as well as a recorded version will be available at:
www.webbertraining.com
www.who.int/gpsc/5may/news/webinars
Epidemiology and Prevention of Bloodstream Infections
1. Pathogenesis
2. Definition
3. Epidemiology
4. Risk factors
5. Procedural Interventions
6. Technical Interventions
7. Summary
Epidemiology and Prevention of Bloodstream Infections
1. Pathogenesis
2. Definition
3. Epidemiology
4. Risk factors
5. Procedural Interventions
6. Technical Interventions
7. Summary
Sources of intravascular
catheter infection
Intraluminal
from tubes and hubs
Haematogen
from distant sites
Extraluminal
Skin
Vein
from skin
Focus of prevention of
infections
Insertion site
Skin
Vein
Focus of prevention of
infections
Hubs
Tubes
Catheters
Insertion site
Skin
Vein
A. Attachment
B. Irreversible
attachment,
aggregation and
formation of
extracellular matrix
C. Maturation
D. Maximal thickness
E. Detachment of
planktonic bacteria
Schachter. Nature Biotechnology 2005;21:361
Biofilm Formation
Co-factors:
- Fibrinogen1, Fibronectin2
- Calcium3, Magnesium3, Iron3,4
- Production of extracellular matrix5,6
- DNA7
- Stress8*
*subinhibitory concentrations of aminoglycoside on P.aeruginosa & E. coli
1. Mehall. Crit Care Med 2002;30:908
2. Vaudaux. J Infect Dis 1993;167:633
3. Banin. Appl Environ Microbiol 2006;72:2064
4. Rhodes. J Med Microbiol 2007;56:119
5. Falcieri. J Infect Dis 1987;155:524
6. Sheth. Lancet 1985; 2:1266
7. Qin. Microbiology 2007;153:2083
8. Hoffman. Nature 2005;436:1171
The formation of protein layers occurs within seconds of
blood contact with a foreign surface.1
Absorbed fibrinogen (ng/cm2)
Adherent S.aureus (cfu x 103/cm2)
Fibrinogen and S.aureus adherence is reduced on
polyurethane catheters with reduced surface roughness and
hydrophilic properties.2
Soluble fibrinogen (μg/ml)
1. Brash. Ann NY Acad Sci 1987
2. Francois. Biomaterials 1996;17:667
* RMS: root mean square
Roughness (RMS*):
600 Å
(Polyurethane)
Roughness (RMS*):
90 Å
Soluble fibrinogen (μg/ml)
(PVP-coated Pellethane®)
Biofim on a catheter surface
Penetration of antibiotics limited
due to viscous matrix
→ Resistance in lower/inner
sheets of biofilm due to subinhibitory concentrations
webs.wichita.edu
Epidemiology and Prevention of Bloodstream Infections
1. Pathogenesis
2. Definition
3. Epidemiology
4. Risk factors
5. Procedural Interventions
6. Technical Interventions
7. Summary
Epidemiology and Prevention of Bloodstream Infections
BSI-LCBI:
laboratory-confirmed bloodstream infection
1
Patient has a recognized pathogen cultured from 1 or
more blood cultures
and
organism cultured from blood is not related to an
infection at another site
Horan. Am J Infect Control 2008;36:309
Epidemiology and Prevention of Bloodstream Infections
BSI-LCBI:
laboratory-confirmed bloodstream infection
2
Patient has at least 1 of the following signs or symptoms:
fever (>38°C), chills, or hypotension
and
signs and symptoms and positive laboratory results are not related
to an infection at another site
and
common skin contaminant is cultured from 2 or more blood cultures
drawn on separate occasions
Horan. Am J Infect Control 2008;36:309
Central line-associated bloodstream infections - CLABSI
BSI-CSEP: Clinical Sepsis
→ CDC: CSEP may be used only to report primary BSI in neonates
and infants. It is not used to report BSI in adults and children!
Patient <1 year of age has at least 1 of the following clinical signs or
symptoms with no other recognized cause: fever (>38°C rectal),
hypothermia (<37°C rectal), apnoea, or bradycardia
and
blood culture not done or no organisms detected in blood
and
no apparent infection at another site
and
physician institutes treatment for sepsis.
Epidemiology and Prevention of Bloodstream Infections
1. Pathogenesis
2. Definition
3. Epidemiology
4. Risk factors
5. Procedural Interventions
6. Technical Interventions
7. Summary
Epidemiology and Prevention of Bloodstream Infections
Intensive Care Units
National Healthcare Safety Network (NHSN) Report: ICU
Per 1’000
catheter-days
Edwards. Am J Infect Control 2009;37:783
International Nosocomial Infection Control Consortium
report, data summary for 2003-2008: ICU
173 ICUs from: Latin America, Asia, Africa, and Europe
Rosenthal. Am J Infect Control 2010;38:95
Epidemiology and Prevention of Bloodstream Infections
Coronary ICU
Surgical cardiothoracic ICU
Medical ICU
Medical/surgical ICU
Neurosurgical ICU
Surgical ICU
Trauma ICU
179
ICUs from:
NHSN
INICC1
n/1’000 CVC-days
n/1’000 CVC-days
2.8
1.6
2.9
2.4
3.5
2.7
4.6
9.9
1.6
10.6
8.9
13.1
17.1
10.6
Argentina, Brazil, Colombia, Costa Rica, Cuba, India, Kosova, Lebanon,
Macedonia, Mexico, Morocco, Nigeria, Peru, Philippines, Turkey, Uruguay
Rosenthal. Am J Infect Control 2008;36:627
Epidemiology and Prevention of Bloodstream Infections
Europe
United Kingdom
2.8-5.4 per 1000 patients at risk
(84 hospitals; hospital-wide)
Germany
2.1 per 1000 catheter-days
(309 ICUs)
Coello. J Hosp Infect 2003;53:46
Gastmeier. J Hosp Infect 2006;64:16
Epidemiology and Prevention of Bloodstream Infections
Non - Intensive Care Units
University of Geneva Hospitals
Zingg. J Hosp Infect 2009;73:41
Epidemiology and Prevention of Bloodstream Infections
Central Venous Catheter (CVC) Utilization and Catheter-Associated
Bloodstream Infection (CA-BSI) Rates for 4 General Medicine Wards
at a Teaching Hospital in St. Louis, Missouri
Marschall. Infect Control Hosp Epidemiol 2007;28:905
National Healthcare Safety Network (NHSN) Report: non-ICU
Edwards. Am J Infect Control 2009;37:783
Epidemiology and Prevention of Bloodstream Infections
Catheter Types
Incidence density
Events per 1000 device-days
Central venous catheter (CVC)
2.7/1000 catheter-days
PICCs
2.1/1000 catheter-days
Tunneled CVCs
1.6/1000 catheter-days
Peripheral venous catheters
0.5/1000 catheter-days
Implantable port systems
0.1/1000 catheter-days
Maki. Mayo Clin Proc 2006;81:1159
Risk for
CLABSI
Incidence density
CVC (2.7‰)
>>
Port system (0.1‰)
…However, in proportions:
CVC (4.4%)
Maki. Mayo Clin Proc 2006;81:1159
≈
Port system (3.6%)
Incidence density
CVC (2.7‰)
>>
Peripheral lines (0.5‰)
…However, in absolute numbers:
CVC
≈
Zingg. Int J Antimicrob Agents 2009;34:S38
Pujol. J Hosp Infect 2007;67:22
Peripheral lines
Epidemiology and Prevention of Bloodstream Infections
Time to infection: CVC
ICU
Zingg. Crit Care Med 2009;37:2167
Zingg. J Hosp Infect 2009;73:41
Non-ICU
Epidemiology and Prevention of Bloodstream Infections
Time to infection: port systems
→ Adults:
median of 80 days
→ Children:
mean of 100 days
Port systems
Tunneled CVCs
Chang. Am J Infect Control 2003;31:34
Adler. J Hosp Infect 2006;62:358
Epidemiology and Prevention of Bloodstream Infections
1. Pathogenesis
2. Definition
3. Epidemiology
4. Risk factors
5. Procedural Interventions
6. Technical Interventions
7. Summary
Epidemiology and Prevention of Bloodstream Infections
Dwell-time
Dwell-time > 7 days

Safdar. Medicine 2002;81:466
Ena. Infect Control Hosp Epidemiol 1992;13:15
Moro. Infect Control Hosp Epidemiol 1994;15:253
RR: 1.0-8.7
Waldvogel: Infections Associated with Indwelling Medical Devices, 3rd Ed.
Epidemiology and Prevention of Bloodstream Infections
Insertion Site
RR
Internal jugular access
Subclavian access
Femoral access
1.0-3.3
0.4-1.0
3.3-4.8
However: no difference of catheter colonization (40.8 vs.
35.7 per 1000 catheter-days) and CLABSI (2.3 vs. 1.5 per
1000 catheter-days) hemodialysis catheters
Parienti. JAMA 2008;299:2413
Goetz. Infect Control Hosp Epidemiol 1998;19:842
Merrer. JAMA 2001:286:700
Ruesch. Crit Care Med 2002;30:454
Epidemiology and Prevention of Bloodstream Infections
Lumen
Zürcher. Anesth and Analg 2004;99:177
Epidemiology and Prevention of Bloodstream Infections
Contaminated intravenous products
There is evidence in the literature about smaller and
larger epidemics with contaminated intravenous
products
Mackel. J Clin Microbiol 1975;2:486
Maki. Am J Med 1976;60:471
Matsaniotis. Infect Control 1984:5:471
Epidemiology and Prevention of Bloodstream Infections
Insertion without using appropriate (maximal)
sterile barrier precautions (MSB)
Sterile gloves, sterile body gown, face mask, head cap, full-size
sterile drape around the insertion site
-
Insertion without MSB1:
 Risk CRBSI  (RR 2.1)
-
Insertion with MSB2:
 Risk CRBSI  (RR 0.2)
1Mermel.
2Raad
Am J Med 1991;91:S197 (Swan Ganz catheters)
II. Infect Control Hosp Epidemiol 1994;15:231
Guidewire exchange
The use of a guidewire for CVC
replacement may be a risk factor
RR: 1.0-3.3
Cobb. New Engl J Med 1992;327:1062
Safdar. Medicine 2002;81:466
Cook. Crit Care Med 1997;25:1417
Epidemiology and Prevention of Bloodstream Infections
Parenteral nutrition
Parenteral nutrition and especially the lipids are
associated with the risk for catheter-associated
bloodstream infection: RR 1.04–4.79
Safdar. Medicine 2002;81:466
Robert. Infect Control Hosp Epidemiol 2000;21:12
Opilla. JPEN J Parenter Enteral Nutr 2007;31:302
Epidemiology and Prevention of Bloodstream Infections
Catheter-related thrombosis
Catheter-related central vein thrombosis is a “frequent”
complication of central venous catheterization in ICU
patients and is closely associated with catheter-related
sepsis: RR 2.62
Timsit. Chest 1998;114:207
Epidemiology and Prevention of Bloodstream Infections
Composition of nursing staff and workload
Lower regular-nurse-to-patient and higher pool
nurse-to-patient ratios (OR 3.4) are risk factors for
CRBSI.
Robert. Infect Control Hosp Epidemiol 2000;21:12
Hugonnet. Crit Care Med 2007;35:76
Epidemiology and Prevention of Bloodstream Infections
Povidone iodine vs. Chlorhexidine
The use of chlorhexidine (2% aqueous or 0.25-0.5
alcohol-based), rather than 10% povidone-iodine for
cutaneous disinfection before insertion of an
intravascular device and for post-insertion site care
can substantially reduce the incidence of device
related infection.
Maki. Lancet 1991;338:339
Mimoz. Crit Care Med 1996;24:1818
Epidemiology and Prevention of Bloodstream Infections
Hand hygiene
Hand hygiene promotion, guided by health care
workers' perceptions, identification of the dynamics of
bacterial contamination of health care workers' hands,
and performance feedback, is effective in sustaining
compliance improvement and is independently
associated with infection risk reduction.
Pessoa-Silva. Pediatrics 2007;120:e382
Zingg. Crit Care Med 2009;37:2167
Epidemiology and Prevention of Bloodstream Infections
1. Pathogenesis
2. Definition
3. Epidemiology
4. Risk factors
5. Procedural Interventions
6. Technical Interventions
7. Summary
Epidemiology and Prevention of Bloodstream Infections
- Hand hygiene
- Maximal sterile barrier precautions
- Chlorhexidine rather than povidone-iodine for
skin antisepsis
- Avoiding femoral access
- Single lumen if possible
- Remove catheter as soon as possible
- Good work organization
- No guidewire exchange
- No routine catheter change
Epidemiology and Prevention of Bloodstream Infections
Multimodal Intervention:
- Education
- Standardized
Processes
- MSB
Eggimann. Lancet 2000;355:1864
-
Chlorhexidine
Hand hygiene
CVC care
Epidemiology and Prevention of Bloodstream Infections
-
2 Intensive care units
2‘104 patients at baseline
1‘050 patients at intervention
13‘200 patient days
Eggimann. Lancet 2000;355:1864
Epidemiology and Prevention of Bloodstream Infections
Eggimann. Lancet 2000;355:1864
Epidemiology and Prevention of Bloodstream Infections
Bundle:
-
Hand hygiene
MSB
Skin antisepsis with chlorhexidine
Avoiding femoral access
Remove of needless CVC
Pronovost. New Engl J Med 2006;355:2725
Epidemiology and Prevention of Bloodstream Infections
-
103 Intensive care units in Michigan
18 Months follow-up
1‘981 Months cumulated
375’757 CVC days
Pronovost. New Engl J Med 2006;355:2725
median/1’000
CVC days
Pronovost. New Engl J Med 2006;355:2725
median/1’000
CVC days
mean/1’000 CVC days: 7.7
Pronovost. New Engl J Med 2006;355:2725
median/1’000
CVC days
mean/1’000 CVC days: 7.7
mean/1’000 CVC days: 1.4
Pronovost. New Engl J Med 2006;355:2725
Epidemiology and Prevention of Bloodstream Infections
Interventions:
- Hand hygiene
- Catheter care
Zingg. Crit Care Med 2009;37:2167
Epidemiology and Prevention of Bloodstream Infections
-
5 Intensive care units
Cohort study
Baseline and intervention
7279 CVC days
Zingg. Crit Care Med 2009;37:2167
Project adoption
Education of head nurses
and teaching nurses
Ex-cathedra teaching
Bedside teaching
Compliance with hand hygiene
→ improvement not impressive…
80
70
60
54
61
68
76
50
%
Preintervention
Postintervention
40
30
20
10
0
Before pt.
contact
Zingg. Crit Care Med 2009;37:2167
After pt. contact
BUT…
After patient contact
Before patient contact
100%
100%
80%
80%
Not
done
60%
Not correct
40%
Correct
60%
40%
20%
20%
0%
0%
Preintervention Postintervention
Not done
Not correct
Correct
Preintervention Postintervention
Baseline
Intervention
Incidence density
(n/1‘000 CVC Tage)
3.9
1.0
Time to infection
(mean SD)
6.52 3.48
9.3 6.63
Zingg. Crit Care Med 2009;37:2167
Time-to-infection
Zingg. Crit Care Med 2009;37:2167
Epidemiology and Prevention of Bloodstream Infections
Interventions:
- CVC care
- Hand hygiene
Huguera. Crit Care Med 2005;33:2022
Epidemiology and Prevention of Bloodstream Infections
- 2 Intensive care units
- 12 Baseline and intervention
- 3,429 CVC days
Huguera. Crit Care Med 2005;33:2022
46.3/1’000
CVC days
19.5/1’000
CVC days
Decrease of CRBSI in a high prevalence setting by
improving hand hygiene and catheter care.
Huguera. Crit Care Med 2005;33:2022
Epidemiology and Prevention of Bloodstream Infections
CVC-bundle
1. Hand hygiene
2. Use of maximal sterile barrier precaution measures at catheter
insertion
3. Skin antisepsis with chlorhexidine-containing products*
4. Subclavian access as the preferred insertion site for nontunnelled catheters
5. Daily review of line necessity with prompt removal of
unnecessary catheters
* e.g. 70% alcohol & 0.5% chlorhexidine-gluconate.
Epidemiology and Prevention of Bloodstream Infections
1. Pathogenesis
2. Definition
3. Epidemiology
4. Risk factors
5. Procedural Interventions
6. Technical Interventions
7. Summary
Catheter colonization
CRBSI1
___________________
__________________
Coating
nCVC RR (95% CI)
nCVC RR (95% CI)
___________________________________________________________________
CHG/silver-sulfadiazine
(external)
2841 0.59 (0.50-0.71)
3016 0.31 (0.06-1.54)
CHG/silver-sulfadiazine
(external/internal)
1070 0.44 (0.23-0.85)
1070 0.70 (0.30-1.62)
Silver, platinum, carbon
720 0.76 (0.57-1.01)
970 0.54 (0.16-1.85)
Minocycline/rifampicin
1063 0.40 (0.23-0.67)
840 0.39 (0.17-0.92)
Chlorhexidine alone
254 1.11 (0.80-1.55)
254 2.37 (0.63-8.96)
Cefazolin
518 0.59 (0.04-7.72)
NA
Vancomycin
176 0.77 (0.63-0.93)
NA
Ramritu. Am J Infect Control 2008;36:104
Epidemiology and Prevention of Bloodstream Infections
Closed system
using collapsible
infusion bags
Rosenthal. Am J Infect Control 2004;32:135
Franzetti. Epidemiol Infect 2009;137:1041
Epidemiology and Prevention of Bloodstream Infections
4 level III ICUs in Buenos Aires, Argentina
608 open systems – 384 closed systems
Rosenthal. Am J Infect Control 2004;32:135
Epidemiology and Prevention of Bloodstream Infections
Meta-analysis: 4 identical interrupted time-series cohort trials
Open fluid containers (glass or semi-rigid plastic) vs closed system (plastic fluid bags)
Methods: open system for 6-9 months followed by exclusive use of
a closed system
Pooled results:
Patients
2237 open system
CLABSI:
Mortality*:
10.1/1000 line-days 3.3 per 1000 line-days (p<0.001)
22.0/100 patients
16.9/100 patients
(p<0.001)
Maki, Rosenthal. ICAAC 2009;K-300
*All-cause mortality
2,136 closed system
Epidemiology and Prevention of Bloodstream Infections
Chlorhexidine-impregnated sponge
Control
Sponge
n/1’000 CVC-days
n/1’000 CVC-days
7.2
3.8
p=0.02
Dwell-times: 15.8 (control), 16.6. (sponge)
Ruschulte. Ann Hematol 2008;88:267
Epidemiology and Prevention of Bloodstream Infections
Chlorhexidine-impregnated sponge
Multicenter randomized controlled trial – ICUs in France
Control
Sponge
n/1’000 CVC-days
n/1’000 CVC-days
1.3
0.4
p=0.004
Timsit. JAMA 2009;301:1231
Epidemiology and Prevention of Bloodstream Infections
Lock solutions
- Taurolidine-citrate
- Ethanol
- Chelators
- Methylene blue
Epidemiology and Prevention of Bloodstream Infections
Lock solutions
Taurolidine
→ In vitro studies: 6
→ In vivo studies: 11 (2 case reports; 7-70 included
patients in cohort or randomized studies
→ 7/11 used taurolidine-citrate 4%
Bradshaw. J Pediatr Gastroenterol Nutr 2008;47:179
Epidemiology and Prevention of Bloodstream Infections
Lock solutions
Controls
TauroLockTM
Patients
Age (median)
90
10.4
89
7.2
Port-days
Tunneled CVC-days
3672
2414
3989
2716
Simon. BMC Infect Dis 2008;8:102
Epidemiology and Prevention of Bloodstream Infections
Lock solutions
Controls
TauroLockTM
Bacteraemia
Bacteraemia with CoNS*
30
14
25
3
ns
0.004
ID all bacteraemia
ID CoNS*
4.9
2.3
3.8
0.5
ns
0.004
More infections with Gram-positives et Gram-negatives!
Results encouraging but not conclusive!
Simon. BMC Infect Dis 2008;8:102
*CoNS: coagulase negative Staphylococcus
Epidemiology and Prevention of Bloodstream Infections
Lock solutions
Ethanol
N=64; many infections among controls
Sanders. J Antimicrob Chemother 2008;62:809
Epidemiology and Prevention of Bloodstream Infections
Lock solutions
Ethanol
Ethanol 40-80% efficient in vitro…
…but results were disappointing in a large
randomized controlled trial (359 catheters*;
4 vs. 5 CLABSI)
*PICCs (249), Hemodialysis catheters (63), Hickman catheters (47)
Crnich. 49th ICAAC 2009; San Francisco
Lock solutions: Chelators
Raad II. Curr Opin Infect Dis 2008;21:385
Lock solutions: Chelators
1
1
1
1
2
Small numbers!
Raad. Curr Opin Infect Dis 2008;21:385
1Minocycline-EDTA
2Trisodium
citrate
Epidemiology and Prevention of Bloodstream Infections
Lock solutions
Citrate - Methylene blue – Paraben*
Sodium-citrate: 7%
Methylene blue: 0.05% + paraben
408 patients with 49,565 catheter-days
(207 controls [heparin]; 201 in C-MB-P group)
C-MB-P*
Controls
0.24/1000 catheter-days
0 patency failure
0.82/1000 catheter-days
4 patency failure
Maki. ICAAC 2009;K-1235
(p=0.005)
(p=0.120)
Luer Activated Device (V-Link®)
Device wall with coating
The proprietary coating process results in
a surface deposition consisting of tightly
bound silver nano-particles that serve as
reservoirs of silver ions.
Controlled
silverrelease
The V-Link device’s VitalShield coating
contains a nano-structure with a surface
layer of Ag2O that controls the release of
Ag+ when in contact with solution.
Silver Nano-Particle Cross-Section
Kindly provided by Baxter
Epidemiology and Prevention of Bloodstream Infections
1. Pathogenesis
2. Definition
3. Epidemiology
4. Risk factors
5. Procedural Interventions
6. Technical Interventions
7. Summary
Zero Central Line Associated
Bloodstream Infections:
…how to get there…
- Multimodal intervention
- Bundle approach
- The “last mile” may require the use of
some technical device (chlorhexidine
patch, coated catheters, impregnated
luer activated device, lock solutions…)
Epidemiology and Prevention of Bloodstream Infections
The most important measures:
Standardized Processes of insertion,
catheter care and catheter removal –
Written Protocols
Epidemiology and Prevention of Bloodstream Infections
The most important measures:
Insertion
- Maximal sterile precautions
- Hand hygiene
- Avoid femoral insertion site
- Checklist (stop CVC insertion procedures if
guidelines are not followed)
Epidemiology and Prevention of Bloodstream Infections
The most important measures:
Good catheter care
- Accurate dressings
- Daily evaluation of CVC and insertion site
- Accurate changing of tubes and hubs
- Remove CVC, as soon as possible
Epidemiology and Prevention of Bloodstream Infections
Thank you